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Artificial Organs Feb 2022Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still... (Review)
Review
INTRODUCTION
Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes.
METHODS
Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion).
RESULTS
Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures.
CONCLUSION
So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed.
Topics: Cost-Benefit Analysis; Humans; Liver Transplantation; Perfusion; Tissue and Organ Procurement
PubMed: 34878658
DOI: 10.1111/aor.14131 -
Current Opinion in Organ Transplantation Jun 2016This article summarizes novel developments in hypothermic machine perfusion (HMP) as an organ preservation modality for kidneys recovered from deceased donors. (Review)
Review
PURPOSE OF REVIEW
This article summarizes novel developments in hypothermic machine perfusion (HMP) as an organ preservation modality for kidneys recovered from deceased donors.
RECENT FINDINGS
HMP has undergone a renaissance in recent years. This renewed interest has arisen parallel to a shift in paradigms; not only optimal preservation of an often marginal quality graft is required, but also improved graft function and tools to predict the latter are expected from HMP. The focus of attention in this field is currently drawn to the protection of endothelial integrity by means of additives to the perfusion solution, improvement of the HMP solution, choice of temperature, duration of perfusion, and machine settings. HMP may offer the opportunity to assess aspects of graft viability before transplantation, which can potentially aid preselection of grafts based on characteristics such as perfusate biomarkers, as well as measurement of machine perfusion dynamics parameters.
SUMMARY
HMP has proven to be beneficial as a kidney preservation method for all types of renal grafts, most notably those retrieved from extended criteria donors. Large numbers of variables during HMP, such as duration, machine settings and additives to the perfusion solution are currently being investigated to improve renal function and graft survival. In addition, the search for biomarkers has become a focus of attention to predict graft function posttransplant.
Topics: Graft Survival; Humans; Hypothermia, Induced; Kidney Transplantation; Organ Preservation; Perfusion; Tissue and Organ Procurement; Treatment Outcome
PubMed: 26945319
DOI: 10.1097/MOT.0000000000000306 -
Transplant International : Official... 2023Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human...
Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48 h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68 years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48 h with all discarded kidneys. Median arterial flow ranged from 405 to 841 mL/min. All kidneys excreted urine until the end of perfusion (median 0.43 mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.
Topics: Humans; Adult; Middle Aged; Aged; Kidney; Kidney Transplantation; Perfusion; Organ Preservation; Extracorporeal Circulation
PubMed: 37901298
DOI: 10.3389/ti.2023.11804 -
Transplantation Jan 2024Normothermic machine perfusion (NMP) aims to preserve organs ex vivo by simulating physiological conditions such as body temperature. Recent advancements in NMP system... (Review)
Review
Normothermic machine perfusion (NMP) aims to preserve organs ex vivo by simulating physiological conditions such as body temperature. Recent advancements in NMP system design have prompted the development of clinically effective devices for liver, heart, lung, and kidney transplantation that preserve organs for several hours/up to 1 d. In preclinical studies, adjustments to circuit structure, perfusate composition, and automatic supervision have extended perfusion times up to 1 wk of preservation. Emerging NMP platforms for ex vivo preservation of the pancreas, intestine, uterus, ovary, and vascularized composite allografts represent exciting prospects. Thus, NMP may become a valuable tool in transplantation and provide significant advantages to biomedical research. This review recaps recent NMP research, including discussions of devices in clinical trials, innovative preclinical systems for extended preservation, and platforms developed for other organs. We will also discuss NMP strategies using a global approach while focusing on technical specifications and preservation times.
Topics: Female; Humans; Organ Preservation; Kidney Transplantation; Liver; Perfusion; Liver Transplantation
PubMed: 37026713
DOI: 10.1097/TP.0000000000004573 -
Surgery Today Mar 2022In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver... (Review)
Review
In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future.
Topics: Aged; Humans; Japan; Liver; Liver Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 33754175
DOI: 10.1007/s00595-021-02265-x -
Best Practice & Research. Clinical... Apr 2017The demand of donor livers for transplantation exceeds the supply. In an attempt to maximize the number of potentially usable donor livers, several centers are exploring... (Review)
Review
The demand of donor livers for transplantation exceeds the supply. In an attempt to maximize the number of potentially usable donor livers, several centers are exploring the role of machine perfusion. This review provides an update on machine perfusion strategies and basic concepts, based on current clinical issues, and discuss challenges, including currently used biomarkers for assessing the quality and viability of perfused organs. The potential benefits of machine perfusion on immunogenicity and the consequences on post-operative immunosuppression management are discussed.
Topics: Animals; Humans; Liver Transplantation; Organ Preservation; Perfusion; Temperature
PubMed: 28624105
DOI: 10.1016/j.bpg.2017.04.001 -
Transplantation Proceedings Nov 2021Most kidney grafts are marginal and from deceased donors, which yield worse clinical outcomes. Hypothermic machine perfusion has created a paradigm shift in kidney... (Review)
Review
Most kidney grafts are marginal and from deceased donors, which yield worse clinical outcomes. Hypothermic machine perfusion has created a paradigm shift in kidney preservation. This mini-review summarizes the main points of hypothermic machine perfusion of kidney transplants that should be known by any physician and surgeon involved with kidney transplantation. Specifically, this review explains a proposed mechanism of action of hypothermic machine perfusion of kidney transplants. This review also describes the clinical effectiveness of hypothermic machine perfusion and explains how to evaluate and predict graft functionality according to machine parameters and perfusate biomarkers. Finally, treatment options and the most recent studies on oxygenated hypothermic machine perfusion are mentioned.
Topics: Humans; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 34696905
DOI: 10.1016/j.transproceed.2021.09.011 -
Current Opinion in Organ Transplantation Apr 2022Ex-vivo machine perfusion has emerged as a promising alternative to static cold storage (SCS) for preservation of liver grafts over the last decade. This review... (Review)
Review
PURPOSE OF REVIEW
Ex-vivo machine perfusion has emerged as a promising alternative to static cold storage (SCS) for preservation of liver grafts over the last decade. This review describes the mechanistic benefits associated with hypothermic machine perfusion (HMP) for preservation of liver grafts and highlights clinical outcomes of liver transplantation using HMP technology.
RECENT FINDINGS
Over the last decade, several single-centre studies have shown decreased biliary complications, decreased early allograft dysfunction (EAD) rates and improved patient survival in liver transplant recipients after application of HMP for liver graft preservation. This has led to initiation of prospective, multicentre, randomized controlled trials (RCTs) in both Europe and North America focused on clinical outcomes in liver transplant recipients using HMP-preserved liver grafts. In addition, recent single-centre studies have shown the utility of perfusate biomarker analysis during HMP in predicting EAD after liver transplantation.
SUMMARY
HMP technology has potential to increase the available donor liver organ pool for liver transplant recipients and improve clinical outcomes after liver transplantation. Broader clinical application of HMP in resuscitation and preservation of liver grafts is anticipated over the next decade once regulatory, logistical and financial challenges are overcome.
Topics: Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 35184093
DOI: 10.1097/MOT.0000000000000973 -
Nature Communications Aug 2023Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion...
Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.
Topics: Humans; Liver Transplantation; Liver; Perfusion; Bile; Preservation, Biological
PubMed: 37553343
DOI: 10.1038/s41467-023-40154-8 -
Nature Medicine Jun 2023Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation... (Randomized Controlled Trial)
Randomized Controlled Trial
Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .
Topics: Humans; Kidney Transplantation; Organ Preservation; Kidney; Perfusion; Tissue Donors
PubMed: 37231075
DOI: 10.1038/s41591-023-02376-7